Lecture 18- Testing for genetic disorders

Question 1

diagnostic prenatal tests

Answer 1

determine if the baby has, or will develop after birth, a particular problem or clinical disorder. condition include syndromes due to changes in chromosome or specific gene mutation/genetic disorders

Question 2

screening prenatal tests

Answer 2

determine if the baby has increased risk of having a particular problem. they are not diagnostic and an increased risk result does not mean the baby will definitely have a problem.

Question 3

clinical indications for prenatal testing

Answer 3

Single gene disorders
• Family history
• Both parent carriers eg cystic fibrosis
• Female carrier eg haemophilia (X linked)
• One parent has an autosomal dominant disorder

Considered at risk of constitutional chromosomal disorder
• Older mother pregnant
• Previous child with significant developmental or
other disorder
• Exposure to chemical or other toxic agent • Abnormal screening test result

Question 4

screening test options

Answer 4

ultrasound and maternal serum analysis to determine whether the baby is at risk

Question 5

Ultrasound scanning

Answer 5

At 8 weeks to check dates, confirm number of
babies
• At 18 weeks detailed scan for anomalies can be done eg anencephaly, cardiac abnormalities
• Safe procedure – no risk to mother or fetus

Question 6

Nuchal translucency

Answer 6

• Measure by ultrasound 10 – 13 weeks pregnancy • Non invasive test
• Combine with maternal serum testing to increase sensitivity and specificity for Down syndrome screening
does not give definitive result only risk of certain problems.

Question 7

maternal serum testing

Answer 7

• Performed at 15 – 17 weeks
• Test for 2-4 feto-placental proteins eg AFP(alpha-feroprotein), β-hCG (human chorionic gonadotrophin), unconjugated estriol (uE3), Inhibin A and pregnancy associated plasma protein A (PAPP-A)
can pick up whether babies have a neural tube defect like spina bifida

Question 8

Chronic Villus sampling

Answer 8

• 10 – 12 weeks of pregnancy
• Obtain fetal cells – analyze chromosomes or DNA • Risk of miscarriage approx 1%
test results take about 1-2 weeks

Question 9

Amniocentesis

Answer 9

• 15-16 weeks of pregnancy
• Collect amniotic fluid which contains fetal cells
• May need to culture cells before analysis
• Miscarriage risk approx 1%

Question 10

laboratory techniques for analysing these cells

Answer 10

FISH eg. for abnormal chromosome number
DNA analysis- usually polymerase chain reaction (PCR) based. can be:
direct mutation analysis if there is one known in family
indirect analysis using a linked or polymorphic marker

Question 11

Fetoscopy and umbilical cord blood

sampling

Answer 11

Performed late in pregnancy Miscarriage risk 2 – 10%
Obtain fetal blood which can be analyzed for:
Karyotype and FISH Gene mutation analysis Metabolic disorders Anaemia

Question 12

issues to consider with pre natal testing

Answer 12

• Not comprehensive testing
• Only test for common chromosome disorders
• Single gene disorders
– Need to know mutation
• Risk of error eg clerical, laboratory testing • Risk (small) to fetus
• Not morally or ethically acceptable to all

Question 13

potential benefits of pre natal testing

Answer 13

• Reassurance when results normal
• Psychological preparation for arrival of
affected baby
• Advance warning for medical team
• Provision of additional information for couple where termination is an option

Question 14

preimplantation genetic diagnosis

Answer 14

when in vitro fertilisation is used, DNA extracted from a cell removed at 6-8 cell stage of embryo can be analysed